Advances and Challenges of the Delayed Brain Development Hypothesis for Attention-Deficit/Hyperactivity Disorder:...

Attention-deficit/hyperactivity disorder (ADHD) is hypothesized to be associated with delayed brain maturation rather than atypical brain development. While this developmental delay hypothesis has gained widespread recognition, research progress has stagnated, and the field lacks a consolidated overview of existing findings and challenges. In this narrative review, we integrate multidimensional findings across behavioral manifestations; electroencephalography; structural, diffusion, and functional magnetic resonance imaging; and genetics, supporting a regionally specific and multitrajectory heterogeneous delay model. Based on a critical discussion of the literature and recent advancements, 4 critical unresolved challenges are identified: 1) incomplete explanatory power of delay phenomena, 2) whether temporal delays lead to reduced peak amplitudes in developmental trajectories, 3) whether delayed trajectories can achieve developmental catch-up prior to brain maturation, and 4) heterogeneity in delayed developmental pathways. To address these challenges, we propose 4 strategies: 1) establishing longitudinal high-density tracking cohorts, 2) constructing multimodal brain age prediction models, 3) identifying neurodevelopmental delay subtypes through heterogeneity modeling, and 4) quantifying ADHD-related developmental delays via disease progression modeling. These approaches are aimed at laying a foundation for precise diagnosis, treatment, and early intervention in ADHD. This review integrates existing evidence on the developmental delay hypothesis to help focus future efforts while highlighting current challenges and potential solutions to inspire innovative directions for research into the neurodevelopmental mechanisms underlying ADHD.